An engineered disulfide bond reversibly traps the IgE-Fc3-4 in a closed, nonreceptor binding conformation.

ABSTRACT: IgE antibodies interact with the high affinity IgE Fc receptor, FcεRI, and activate inflammatory pathways associated with the allergic response. The IgE-Fc region, comprising the C-terminal domains of the IgE heavy chain, binds FcεRI and can adopt different conformations ranging from a closed form incompatible with receptor binding to an open, receptor-bound state. A number of intermediate states are also observed in different IgE-Fc crystal forms. To further explore this apparent IgE-Fc conformational flexibility and to potentially trap a closed, inactive state, we generated a series of disulfide bond mutants. Here we describe the structure and biochemical properties of an IgE-Fc mutant that is trapped in the closed, non-receptor binding state via an engineered disulfide at residue 335 (C

SUBMITTER: Wurzburg BA 

PROVIDER: S-EPMC3476292 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature